Citrate esters and methods

ABSTRACT

Citrate esters are formed utilizing organic titanates as a catalyst allowing excess alcohol to be removed. Four citrate esters have been found which provide advantageous plasticizing properties to PVC compositions which include superior toxicity test results and superior soapy water extraction test results. The four citrate esters are: acetyltri-n-hexyl citrate, n-butyryltri-n-hexyl citrate, acetyltri-n-(hexyl/octyl/decyl) citrate, and acetyltri-n-(octyl/decyl) citrate. Articles formed from the PVC plasticized mixtures are extremely useful in the medical or health care field as they demonstrate a low order of toxicity.

This is a continuation of application Ser. No. 06/735,149 filed May 171985, now abandoned which was a continuation-in-part of application Ser.No. 06/619,583 filed 11 June 1984, also now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

Citrate esters are useful as plasticizers for polyvinyl chloride (PVC)resins as certain of these esters provide a low order of toxicity whencompared to phthalate esters which have been conventionally used. Otheradvantages have been noted using certain citrate esters as plasticizersin PVC compositions and articles, including improved resistance to soapywater extraction and low temperature and transport properties.

The preparation of the citrate esters has been found to be significantlyenhanced by the utilization of certain organic titanate catalysts whichallow the excess alcohol to be removed after the esterification step.

2. Description of the Prior Art and Objectives of the Invention

Citrate esters commercially produced using citric acid have long beenavailable and have been used as plasticizers for PVC resins. However,the performance of articles produced from the PVC resin compositionswhether utilizing citrate esters known to date or conventional phthalateplasticizers have had many inherent disadvantages. For example,medical-grade PVC compositions are used to form blood bags, tubing and avariety of health-related articles and in recent years toxicity has beena major concern for manufactures of such articles. Recent reports haveidentified di-2-ethylhexyl phthalate (DEHP) or (DOP) anddi-2-ethyl-hexyl adipate (DEHA) as hepatocarcinogens in rodents. Whilecertain of the phthalates have excellent plasticizing qualities, theirsuspected carcinogenic nature renders them doubtful candidates forfuture medical-grade uses. As an alternative, known citric acid esterssuch as acetyltri-n-butyl and tri-n-butyl citrate were tried as PVCplasticizers in medical-grade applications but it was determined thatthese compounds were not entirely satisfactory due to their high soapywater extraction percentages and would therefore not be useful in manymedical area applications. Also, it has been found that new productiontechniques had to be devised for the newer citric acid esters which weredetermined to have suitable toxicity and physical characteristics whenused as PVC plasticizers.

It is therefore an objective of the present invention to provide PVCplasticizers which provide superior toxicity test results in biologicalstudies.

It is also an objective of the present invention to provide plasticizersfor PVC compositions which can be processed without difficulty usingconventional extrusion, calendering, or plastisol techniques.

It is yet another objective of the present invention to provide newcitric acid esters namely: acetyltri-n-hexyl citrate,n-butyryltri-n-hexyl citrate, acetyltri-n-(hexyl/octyl/decyl)citrate,and acetyltri-n-(octyl/decyl)citrate which can be used as plasticizershaving desirable physical characteristics when imparted into PVCcompositions.

It is still another objective of the present invention to provide PVCcompositions and formed articles therefrom having superior results intoxicology studies concerning dermal toxicity, oral toxicity and geneticassays.

It is also an objective of the present invention to provide a newprocess for the low temperature manufacture of the four new citric acidesters utilizing organic titanates to provide economical and efficientproduction methods. be demonstrated to those skilled in the art as setforth in detail below.

SUMMARY OF THE INVENTION

Citrate esters of the formula: ##STR1## where R₁, R₂, and R₃ =CH₃ to C₁₈H₃₇

R₄ =CH₃ to C₇ H₁₅

and more specifically acetyltri-n-hexyl citrate, n-butyryltri-n-hexylcitrate, acetyltri-n-(hexyl/octyl/decyl)citrate, andacetyltri-n-(octyl/decyl)citrate are produced utilizing an organictitanate catalyst and such esters have been found useful asmedical-grade plasticizers in PVC compositions. The plasticizers have alow order to toxicity and inpart to PVC the proper balance of physicalproperties needed in health care and medical-grade uses. The productionsteps for the citric acid esters include low temperature esterificationat 140° C. or below, removal of any excess alcohol and thereafter,alkoxylation. Conventional neutralization and finishing steps are thencarried out. The alkoxylation step is carried out at a temperature lessthan approximately 110° C.

A PVC resin can be combined with one of the above-mentioned citric acidesters, along with suitable stabilizers and lubricants, to form aplasticized PVC which can be extruded, calendered or otherwise processedinto suitable articles of manufacture including blood bags, tubing andother products. Articles so made have a low order of toxicity andprovide superior extraction properties, particularly in soapy waterextraction tests. The soapy water extraction test is a standard test,the results of which closely resemble the results obtained with bodyfluids such as human blood.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The four preferred forms of the citrate esters are as follows: ##STR2##

The preferred method of manufacture of the above-identified citrateesters comprises low temperature esterification below 150° C. andpreferably at a temperature range of from 125° C. to 130° C. of theproper alcohol (such as n-hexyl alcohol for acetyltri-n-hexyl citrate)with citric acid in the presence of the organic titanate, tetra-n-butyltitanate, removal of any excess n-hexyl alcohol, and then alkoxylationof the esters produced with an acid anhydride. At esterificationtemperatures above 150° C. citrates undergo rapid degradation resultingin numerous products of decomposition. At temperatures somewhat below150° C. the major decomposition product is an aconitate ester. Thealkoxylation takes place at a temperature of below approximately 110° C.Tetra-n-butyl titanate is preferred since the ester interchange whichtakes place between the titanate alkyl groups and citrate alkyl groupsdoes not result in the introduction of alkyl groups not normally presentin the citrate esters.

The preferred PVC composition comprises blending and milling a mediummolecular weight PVC resin with one of the above citrate esters on a twoto one ratio, resin to plasticizer, along with stabilizers, lubricantsand extenders as required. Articles manufactured from the preferred PVCcompositions include blood bags, tubing and other articles for themedical and health care fields.

DETAILED DESCRIPTION OF THE INVENTION

Certain citrate esters, namely acetyltri-n-hexyl citrate,n-butyryltri-n-hexyl citrate, acetyltri-n-(hexyl/octyl/decyl)citrate andacetyltri-n-(octyl/decyl)citrate have been found to be particularlyuseful in medical applications when compounded with PVC resins throughconventional plastisol, calendering or extrusion techniques. Suchplasticized PVC exhibits good clarity, good low temperature properties,low volatility and low extractability into various media. Also, a loworder of acute toxicity has been shown and complete compatibility withmedium molecular weight PVC resins make the four named esters unique andvaluable. Studies have shown that the four citrate esters are not toxicsubstances, primary skin irritants or ocular irritants to unrinsed eyesand oral administration has produced no signs of systemic toxicity andhas shown no mortality in fasted mice or rats. Genetic toxicology assaysfor detecting mutagenic activity at the gene or chromosomal level haveshown that these esters do not induce gene mutation in either microbialcells or in mammalian cells in vitro or chromosomal mutation in vivo orin vitro. Studies have also shown that under in vivo conditions, thesecitrate esters hydrolyze rapidly and completely in concentrations atexpected realistic levels of human exposure.

Preparation of the citrate esters are as follows:

Example 1 Preparation of acetyltri-n-hexyl citrate

330 lbs. of n-hexyl alcohol, 180 lbs. of citric acid and 1.54 lbs. oftetra-n-butyl titanate and 15 gallons of heptane are charged to a vesselequipped with agitator, thermometer, vapor column, condenser and adecanter set to allow removal of water formed during the reaction whilerefluxing heptane. The esterification is effected at 140° C. to maintainthe aconitate (THA) level below 0.5% for general production. As shown inFIG. 1 the aconitate level can be kept well below the 0.2% range bylonger reaction times at lower temperatures with the optimum time, andaconitate levels reached by temperatures of from approximately 125° C.to 130° C. As shown, at a temperature of approximately 130° C. a uniqueresult is achieved in that the aconitate formation levels out to providea citrate ester having excellent purity. During esterification water isperiodically removed from the decanter in order to maintain propertemperature and reaction rates. The esterification is continued untilthe esterification mixture tests 0.5% maximum acidity calculated ascitric acid although lower temperature esterification and aciditypercentage may be used for higher purity products as mentioned above.Next, the vessel is cooled to 120° C. and any water is removed from theseparator and any heptane therein is also removed for future use. Thereflux line of the vessel is closed and pressure on the system isreduced slowly. The kettle is heated to 130°-140° C. and steam isintroduced to help remove any residual alcohol. This vacuum streamstripping is continued until alcohol cannot be detected by conventionallaboratory tests. When no more alcohol can be found, the steam isdiscontinued and the temperature is reduced to 100° C. and the vacuum isbroken with nitrogen gas.

Next, 0.4 lb. concentrated sulfuric acid (H₂ SO₄) is charged into thevessel after which it is sealed and approximately 107 lbs. of aceticanhydride (in a determined molar amount) are added at a slow rate sothat the temperature does not exceed 110° C. When all the anhydride hasbeen added, agitation of the mix continues for approximately one houruntil the acetylation reaction has been completed.

Next, a full vacuum is put on the system and enough heat is added fordistillation to proceed at a suitable rate. This step continues untilacetic acid is shown to be 5% or less by conventional lab testswhereupon the mixture is cooled to 75° C. for neutralization.

The remaining steps of neutralization, bleaching, washing, etc. arecarried out as in conventional esterification processes.

Example 2 Preparation of n-butyryltri-n-hexyl citrate

The vessel used in example 1 is again charged with 330 lbs. of n-hexylalcohol, 180 lbs. of citric acid and 1.54 lbs. of tetra-n-butyltitanate. Esterification is carried out as in example 1 as is theheptane-alcohol strip. Butyrylization is thereafter done with theaddition of 0.4 lbs. of concentrated sulfuric acid and 166 lbs. ofn-butyric anhydride as shown above in the acetylation process. Thebutyric acid may be removed as shown above or by neutralization.

Examples 1 and 2 produce esters with the following characteristics:

    ______________________________________                                        ANALYTICAL DATA                                                                            Acetyltri-n-hexyl                                                                           n-Butyryltri-n-hexyl                               Property     Citrate       Citrate                                            ______________________________________                                        Purity wt %  99            99                                                 Color APHA   50 max.       50 max                                             Neut. No. mg KOH/g                                                                         0.2 max.      0.2 max.                                           Moisture K.F.                                                                              0.25 max.     0.25 max.                                          S.G. @ 25/25° C.                                                                    1.0045-1.0055 0.991-0.995                                        R.I. @ 25/25° C.                                                                    1.445-1.447   1.444-1.448                                        Viscosity @ 25° C. cps                                                              25-35         25-35                                              Odor @ 25° C.                                                                       Little or none                                                                              Little or none                                     Heat Stability                                                                (2 Hrs. @ 150° C.)                                                     Color APHA   50-60         50-60                                              Neut. No. mg KOH/g                                                                         0.2 max.      0.2 max.                                           Odor @ 25° C.                                                                       Mild          Mild                                               ______________________________________                                    

It has been determined that a citrate ester yield can be achieved of99+% purity with a minimum of aconitate formation and unaceylated estersby lowering the esterification temperatures to 130° C. or below with apreferable temperature range of 125° C. to 130° C. Table A and FIG. 1demonstrate the percentage of tri-n-hexyl aconitate (THA) formed duringthe production of acetyltri-n-hexyl citrate whereby the reaction isterminated at approximately 0.2% acidity, as citric acid. As shown inTable A and FIG. 1 below, the aconitate levels range from approximately0.14 to 0.19 with a reaction time of from 25 to 19 hours at temperaturesof from 125° C. to 130° C. It has been determined that by lowering thetemperature from 140° C. to 130° C. an additional reaction time of only90 minutes is required with the aconitate level dropping from 0.35 to0.19%, a decrease of approximately 45%. As shown, the aconitate levelcan be tremendously decreased by lowering the temperature approximately10 degrees from 140° C. to 130° C. without substantially increasing thereaction time based on 0.2% acidity (citric acid) as the reactioncompletion indicator. As shown in FIG. 1 a stabilization of theaconitate formation occurs during esterification at a criticaltemperature of approximately 130° C. providing a technique for themanufacture of high purity esters having low aconitate levels. Loweraconitate percentages and other impurities provide the high qualityplasticizer needed for medical-grade products.

                  TABLE A                                                         ______________________________________                                        Reaction Time and Aconitate                                                   Formation Rates at Various Temperatures                                       Esterification                                                                            Reaction   Final THA  % Acidity As                                Temperature (°C.)                                                                  Time (Hrs.)                                                                              Content (%)                                                                              Citric Acid                                 ______________________________________                                        120          241/4     0.07       0.17                                        125         25         0.14       0.17                                        130         19         0.19       0.17                                        140          171/2     0.41       0.16                                        150         13         0.59       0.19                                        ______________________________________                                    

It is believed that acids such as citric acid with low pK values exhibita synergistic effect with titanate catalysts at low temperatures in the150° C. or lower range. Phthalic acid which has a high pk value will notundergo esterification with the titanate catalysts at these lowtemperatures.

Also, other organic titanate catalysts can be used to produce the four(4) esters of this invention such as tetrakis-2-ethylhexyl titanatealthough superior results have been demonstrated using tetra-n-butyltitanate.

    ______________________________________                                        PREPARATION AND TESTING OF PVC COMPOSITIONS                                                           PARTS BY                                              FORMULATION             WEIGHT                                                ______________________________________                                        Resin (Medium Molecular Weight PVC)                                                                   100                                                   Plasticizer             50                                                    Stabilizer (Calcium/Zinc)                                                                             2.5                                                   Lubricant (stearic acid)                                                                              0.25                                                  ______________________________________                                    

The above formulation was blended and milled for 5-10 minutes at 325° to340° F. The milled stock was pressed (3 min. at 340°-360° F. and 32,000psi) to 40- and 70-mil sheets, and aged for 48 hours at room temperaturefor evaluation. All tests were made with samples cut from 70-mil pressedstock except for extraction tests which were obtained on 40-mil samples.The performance data was obtained by accepted ASTM methods withmodifications as detailed below in Table B.

    ______________________________________                                        Tensile Strength                                                                             Determined with Instron TT, 1100                               Ultimate Elongation                                                                          series (2 in./min.) using a                                    Modulus (100% elongation)                                                                    dumbbell-shaped specimen. Test                                 (ASTM D638)    carried out at 70° ± 5° F.                    Hardness       Determined with Shore Durometer A                              (ASTM D676)    (10 sec.) at 75° ± 5° F.                      Torsional Flex (T.sub.4 and T.sub.f)                                                         Determined with Torsion Flex                                   (ASTM D1043)   Tester suspended Clash and Berg design.                                       T.sub.4 is the temperature at which                                           the Modulus of Rigidity is 10,000                                             psi; T.sub.f is the temperature at                                            which the Modulus of Rigidity is                                              100,000 psi.                                                   Brittle Point  Determined by impact method using                              (ASTM D746)    Scott Tester, Model E                                          Volatile Loss (A/C)                                                                          Determined on specimens 2 inches in                            (ASTM D1203)   diameter heated in activated carbon                                           at 70° C. for 24 hours. Results                                        are expressed as percent of plasticizer                                       lost.                                                          Water extraction (Tap)                                                                       Determined on specimens 2 inches in                            Soapy Water Extraction                                                                       diameter suspender in appropriate                              (1% Ivory Flakes)                                                                            liquid at 60° C. for 24 hours.                          Oil Extraction Results are expressed as percent                               (ASTM NO. 3)   of plasticizer lost.                                           Migration Loss (silica)                                                                      Determined on specimens 2 inches in                                           diameter heated in silica (100 mesh),                                         at 70° C. for 24 hours. Results                                        are expressed as percent or plasticizer                                       lost.                                                          Volatile Loss (air)                                                                          Determined by Oven Method (24 hr. at                                          100° C.) on specimens 2 inches in                                      diameter. Results are expressed as                                            percent of plasticizer lost.                                   ______________________________________                                    

                                      TABLE B                                     __________________________________________________________________________    (PLASTICIZER PERFORMANCE DATA)                                                PLASTICIZER     DEHP DEHA #1   #2   #3   #4   #5                              __________________________________________________________________________    HARDNESS,       79   78   78   81   81   87   87                              Durometer A, 10 Sec.                                                          TENSILE, psi    2748 1797 2862 2978 2924 2743 2789                            ULTIMATE        395  414  400  390  427  364  374                             ELONGATION, %                                                                 100% MODULUS, psi                                                                             1368 1092 1348 1574 1362 1656 1704                            T.sub.4 (10,000 psi),                                                                         -8.4 -30.8                                                                              -7.6 -9.1 -11.9                                                                              -6.9 -4.0                            °C.                                                                    T.sub.f (100,000 psi),                                                                        -38.8                                                                              -66.5                                                                              -35.6                                                                              -41.6                                                                              -48.7                                                                              -53.1                                                                              -59.7                           °C.                                                                    BRITTLE POINT, °C.                                                                     -24.5                                                                              -56.5                                                                              -18.5                                                                              -26.0                                                                              -33.5                                                                              -36.8                                                                              -37.8                           VOLATILE LOSS, (air), %                                                                       4.8  7.1  12.1 2.6  1.7  .3   .1                              VOLATILE LOSS, (A/C), %                                                                       3.4  7.6  7.0  1.7  1.4  2.8  4.5                             WATER EXTRACTION, %                                                                           .7   1.5  1.2  1.9  1.7  1.5  3.3                             SOAPY WATER     2.7  11.0 9.5  5.4  2.2  3.4  2.4                             EXTRACTION, %                                                                 OIL EXTRACTION, %                                                                             11.4 34.7 10.9 13.8 15.7 15.2 19.3                            SILICA GEL MIGRATION, %                                                                       12.2 23.0 17.0 4.4  3.6  4.8  7.4                             __________________________________________________________________________     #1  acetyltrin-butyl citrate                                                  #2  acetyltrin-hexyl citrate                                                  #3  nbutyryltri-n-hexyl citrate                                               #4  acetyltrin-(hexyl/octyl/decyl) citrate                                    #5  acetyltrin-(octyl/decyl) citrate                                     

The plasticizer performance data in Table C demonstrates the results oftests with citric esters/expoxidized soybean oil (ESO) blends. ESO iscommonly used in conjunction with DEHP at levels in the range of 1-5%based on DEHP as an aid in stabilization. The ratio of 2.5/97.5ESO/citrate was used as a base point in the studies. Test results onthis combination are shown in column 1. A significant improvement inproperties, particularly soapy water extraction is noted.

                                      TABLE C                                     __________________________________________________________________________    (PLASTICIZER PERFORMANCE DATA)                                                PLASTICIZER     2.5 ESO                                                                            20 ESO                                                                             40 ESO                                                                             40 ESO                                                                             40 ESO                                    PERCENTAGES:    97.5 #2                                                                            80 #2                                                                              60 #2                                                                              60 #3                                                                              60 #5                                     __________________________________________________________________________    HARDNESS,       81   80   80   81   85                                        Durometer A, 10 Sec.                                                          TENSILE, psi    2907 3010 3079 3165 3097                                      ULTIMATE        422  424  420  428  395                                       ELONGATION, %                                                                 100% MODULUS, psi                                                                             1415 1429 1491 1514 1779                                      T.sub.4 (10,000 psi)                                                                          -9.5 -7.8 -7.7 -8.2 -5.4                                      °C.                                                                    T.sub.4 (100,000 psi)                                                                         -41.8                                                                              -41.3                                                                              -39.3                                                                              -41.8                                                                              -50.3                                     °C.                                                                    BRITTLE POINT, °C.                                                                     -26.5                                                                              -25.5                                                                              -20.5                                                                              -24.5                                                                              -26.5                                     VOLATILE LOSS, (Air), %                                                                       2.4  2.1  1.5  .8   .5                                        VOLATILE LOSS, (A/C), %                                                                       1.3  1.6  1.4  .9   1.1                                       WATER EXTRACTION, %                                                                           1.3  .9   .6   .8   1.0                                       SOAPY WATER     2.9  2.9  6.4  4.8  3.8                                       EXTRACTlON, %                                                                 OIL EXTRACTION, %                                                                             13.0 11.6 10.1 10.0 12.9                                      SILICA GEL MIGRATION, %                                                                       5.7  5.3  4.7  4.0  2.5                                       __________________________________________________________________________     ESO  Ester/epoxidized Soybean Oil                                             #2  acetyltrin-hexyl citrate                                                  #3  nbutyryltri-n-hexyl citrate                                               #5  acetyltrin-(octyl/decyl) citrate                                     

Since ESO is less expensive than citrates, a reduction in plasticizercost results if ESO can be substituted for part of the citrates. Resultsof tests with higher ESO/citrate ratios as shown in columns 2-5 of TableC and a significant improvement in properties up to and perhaps beyondthe ratio of 20/80 ESO/citrate ratio as shown.

Various other PCV compositions can be formulated and the examples andillustrations shown herein are for illustrative purposes and are notintended to limit the scope of the invention.

I claim:
 1. A polyvinyl chloride composition comprising a polyvinylchloride resin and a plasticizing amount of n-butyryltri-n-hexylcitrate, said n-butyryltri-n-hexyl citrate having heat stabilitycharacteristics, when tested at 150° C. for two hours, of a color notgreater than 50-60 apha, and a mild odor at 25° C., and also having anaconitate level of less than about 0.2% when the esterification mixturefrom which said citrate is produced tests 0.5% maximum aciditycalculated as citric acid.
 2. A polyvinyl chloride composition asclaimed in claim 1 wherein said citrate has a low order to toxicity. 3.A polyvinyl composition as claimed in claim 1 wherein said citrate hasan additional heat stability characteristics, after heating at 150° C.for two hours, of a neutralization number, MG KOH/G, of not greater thanabout 0.2.
 4. A medical article formed from a polyvinyl chloridecomposition comprising a polyvinyl chloride resin, a plasticizing amountof n-butyryltri-n-hexyl citrate, a stabilizer and a lubricant, saidcitrate having heat stability characteristics, after heating at 150° C.for two hours, of a color not greater than 50-60 apha, and a mild odorat 25° C., and also having an aconitate level of less than about 0.2percent when the esterification mixture from which said citrate isproduced tests 0.5 percent maximum acidity calculated as citric acid. 5.A medical article as claimed in claim 4 comprising a blood bag.
 6. Amedical article as claimed in claim 5, wherein said citrate has a loworder of toxicity.
 7. A medical article as claimed in claim 5, whereinsaid citrate has an additional heat stability characteristic, afterheating at 150° C. for two hours, of a neutralization number, MG KOH/G,of not greater than about 0.2
 8. A method of producing acetyltri-n-hexylcitrate comprising the steps of: heating n-hexyl alcohol and citric acidin the presence of an organic titanate at a temperature of approximately140° C. to effect esterification, removing the excess n-hexyl alcohol,and acetylating the ester by adding acetic anhydride and sulfuric acidwhile maintaining the temperature below approximately 110° C. until theacetylation reaction is complete, wherein the acetyltri-n-hexyl citrateproduced has heat stability characteristics, after heating at 150° C.for two hours, of a color not greater than 50-60 apha, and a mold odorat 25° C.
 9. A method as claimed in claim 8 wherein said organictitanate is tetra-n-butyl titanate.
 10. A method of producingn-butyryltri-n-hexyl citrate comprising the steps of: heating n-hexylalcohol and citric acid in the presence of an organic titanate at atemperature of approximately 140° C. to effect esterification, removingthe excess n-hexyl alcohol, and butyrylating the ester by addingsulfuric acid and n-butyric anhydride while maintaining the temperaturebelow approximately 110° C. until the butyrylation reaction is complete,wherein the n-butyryltrin-n-hexyl citrate produced has heat stabilitycharacteristics, after heating at 150° C. for two hours, of a color notgreater than 50-60 apha, and a mild odor at 25° C.
 11. A method ofproducing n-butyryltri-n-hexyl citrate as claimed in claim 10 whereinthe excess n-hexyl alcohol is removed by vacuum steam stripping.
 12. Amethod as claimed in clam 10 wherein said organic titanate istetra-n-butyl titanate.
 13. A method of producing acetyltri-n-hexylcitrate comprising the steps of: heating n-hexyl alcohol and citric acidin the presence of an organic titanate at a temperature not greater thanapproximately 130° C. to effect esterification, removing the excessn-hexyl alcohol, and acetylating the ester by adding acetic anhydrideand sulfuric acid while maintaining the temperature below approximately110° C. until the acetylation reaction is complete, wherein theacetyltrin-n-hexyl citrate produced has heat stability characteristics,after heating at 150° C. for two hours, a color not greater than 50-60apha, and a mild odor at 25° C., and also has an aconitate level of lessthan about 0.2 percent when the esterification mixture from which saidcitrate is produced tests 0.5 percent maximum acidity when calculated ascitric acid.
 14. A method of producing acetyltri-n-hexyl citrate asclaimed in claim 13 wherein said organic titanate is tetra-n-butyltitanate.
 15. A method of producing n-butyryltri-n-hexyl citratecomprising the steps of: heating n-hexyl alcohol and citric acid in thepresence of an organic titanate at a temperature not greater thanapproximately 130° C. to effect esterification, removing the excessn-hexyl alcohol, and butyrylating the ester by adding sulfuric acid andn-butyric anhydride while maintaining the temperature belowapproximately 110° C. until the butyrylation reaction is complete,wherein the n-butyryltri-n-hexyl citrate produced has heat stabilitycharacteristics, after heating at 150° C. for two hours, of a color notgreater than 50-60 apha, and a mild odor at 25° C., and also has anaconitate level of less than about 0.2 percent when the esterificationmixture from which said citrate is produced tests 0.5 percent maximumacidity when calculated as citric acid.
 16. A method of producingn-butyryltri-n-hexyl citrate as claimed in claim 15 wherein said organictitanate is tetra-n-butyl titanate.